We have previously discovered a new strain of actinomycetes, Streptomyces tenjimariensis SS-939 which was deposited in the Japanese public depository "Fermentation Research Institute" under the deposit number FERM-P 4932 and in the American Type Culture Collection under ATCC Number 31603, and produced by cultivation of said strain several different new aminoglycosidic antibiotic substances, istamycin A, istamycin B, istamycin A.sub.O and istamycin B.sub.O (refer to our Japanese Patent KOKAI No. 145697/80 and No. 43295/81; our published U.K. Patent Application GB 2,048,855A; and our allowed U.S. patent application Ser. No. 141,492, filed Apr. 18, 1980, now U.S. Pat. No. 4,296,106). Subsequently, we totally synthesized di-N.sup.6',O.sup.3 -demethylistamycin A and found its antibacterial activity against Pseudomonas aeruginosa to be significantly higher than that of istamycin A (refer to Japanese Patent Application No. 38889/80; U.K. Patent Application 8108886; U.S. patent application Ser. No. 241,649, now abandoned). We than continued our studies on istamycin antibiotics with the intention of converting istamycin B (which has a higher antibacterial activity than istamycin A) into the 3-O-demethyl derivative thereof, and have now succeeded in synthesizing 3-O-demethylistamycin B starting from istamycin B.sub.O, and have found that 3-O-demethylistamycin B is effective against not only Pseudomonas aeruginosa but also a variety of resistant bacteria. In this series of studies, we have also synthesized 3-O-demethylistamycin B.sub.O and 3-O-demethyl-2"-N-formimidoylistamycin B, the former being useful as an intermediate to be converted into 3-O-demethylistamycin B by glycylating the 4-methylamino group thereof, and the latter being a 3-O-demethylistamycin B derivative useful as an antibiotic similarly to formimidoylistamycin B and formimidoylistamycin A (see Japanese Patent Application No. 41184/80; Japanese Patent Application No. 107201/80; U.K. Patent Application No. 8108602; and U.S. patent application Ser. No. 244,232, now U.S. Pat. No. 4,382,926) both of which were synthesized by us.
The 3-O-demethylistamycin B.sub.O, 3-O-demethylistamycin B and 3-O-demethyl-2"-N-formimidoylistamycin B described and claimed herein have been disclosed by us in J. Antibiotics, 33, 1577-1580 (December 1980), along with details of their preparation and their antibacterial activity.
We are aware of U.S. Pat. No. 4,255,421 which discloses certain O-demethylaminoglycosides and claims those of the formula ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and are hydrogen or methyl, R.sub.3 is hydrogen or an unsubstituted or substituted aminoacyl group having 2 to 4 carbon atoms in the acyl moiety, the substituent being selected from hydroxy, formyl and carbamoyl; provided that, when R.sub.1, R.sub.2 and R.sub.3 are each hydrogen atoms, the methylamino group at the 4-position is not oriented trans to the hydroxyl groups at the 3- and 5-positions.
Although the aminocyclitol rings are numbered in the opposite directions in U.S. Pat. No. 4,255,421 and in the compounds disclosed and claimed herein (compounds named as 3-O-demethyl derivatives herein are named as 5-O-demethyl derivatives therein), it may be seen that the claims of U.S. Pat. No. 4,255,421 literally include within their scope two of the three compounds disclosed and claimed herein, i.e. 3-O-demethylistamycin B.sub.O and 3-O-demethylistamycin B. However, U.S. Pat. No. 4,255,421 does not exemplify either of these two compounds and, further, neither discloses the starting material necessary for their preparation nor teaches how the necessary starting material may be prepared. Thus, 3-O-demethylistamycin B.sub.O and 3-O-demethylistamycin B contain a 6'-N-methyl group and a C-1 amino group which is cis to the sugar moiety, and the starting material for the demethylation reaction (istamycin B.sub.O herein) must contain these same groups and configurations. U.S. Pat. No. 4,255,421, on the other hand, discloses as starting materials only antibiotic complex KA-6606 [the sporaricins; see J. Antibiotics, 32, 187 (1979)], at least some of which contain a C-1 amino group that is cis to the sugar moiety, but all of which have a 6'-C-methyl group; antibiotic complex KA-7038 [the sannamycins; see J. Antibiotics, 32, 1066 (1979)], some of which contain a 6'-N-methyl group but all of which have a C-1 amino group which is trans to the sugar moiety; and fortimicins A and B [see J. Antibiotics, 30, 552 (1977)], both of which have a 6'-C-amino group and a C-1 amino group which is trans to the sugar moiety, as well as an additional hydroxyl group on the C-6 position (numbered C-2 herein) which is not present in the compounds claimed herein. Thus, the sporaricin, sannamycin and fortimicin starting materials disclosed in U.S. Pat. No. 4,255,421 are not suitable starting materials for the preparation of any of the three compounds disclosed and claimed herein, since they have the wrong 6'-substitution and/or the wrong stereo configuration of the 1-amino group, and in some instances have an additional hydroxyl group on the C-6 position. The starting materials disclosed in U.S. Pat. No. 4,255,421 are products of fermentation and not synthetic products, and there is no disclosure of how to obtain the necessary starting materials for the preparation of the compounds disclosed and claimed herein. Thus, U.S. Pat. No. 4,255,421 does not contain an enabling disclosure for the preparation of the herein claimed 3-O-demethylistamycin B.sub.O, 3-O-demethylistamycin B or 3-O-demethyl-2"-N-formimidoylistamycin B.